Alcohol tolerance refers to a diminished intensity of response as doses are repeated. Tolerance has long been implicated as a factor contributing to alcohol abuse and dependence by encouraging the use of escalating doses to reinstate initial effects of the drug. Alcohol is also well-known for its acute impairing effects on neurocognitive processes involved in the regulation of behavior and attention. Yet, little research has examined how such disturbances might reduce self-control over actual alcohol use, leading to patterns of abusive drinking (e.g., binge drinking). Moreover, despite interest in tolerance as a phenotypic marker for alcohol use disorders, little research has sought to determine how differences in alcohol sensitivity and tolerance might characterize populations at-risk for alcohol abuse, such as those with externalizing disorders (e.g., ADHD). The proposal is based on the working hypothesis that abuse potential of alcohol is determined by sensitivity to its reward-enhancing effects and to its disinhibiting effects. The proposed studies examine the contribution of tolerance to abuse potential as measured by changes in alcohol effects on basic mechanisms involved in the control and regulation of behavior. Studies will investigate: 1) the sensitivity of control mechanisms to the impairing effects of alcohol and their contribution to abuse potential;2) tolerance development to the impairing effects on mechanisms that control behavior and attention;3) the contribution of such tolerance to the abuse potential of alcohol;4) the degree to which the inhibitory and attentional deficits associated with ADHD influence alcohol sensitivity and the development of tolerance;and 5) the degree to which the developmental course of tolerance is affected by concomitant use of stimulant drugs commonly used in the management of ADHD.

Public Health Relevance

Excessive alcohol use contributes to many adverse health consequences (e.g., alcohol poisoning, acute alcoholic hepatitis and liver cirrhosis). Tolerance has long been implicated as a factor contributing to alcohol abuse and dependence by encouraging the use of escalating doses to reinstate initial effects of the drug. Yet, little research has examined how tolerance might increase the risk for alcohol abuse. The proposed studies examine the contribution of tolerance to abuse potential as measured by changes in the ability of the drug to alter basic mechanisms involved in the control and regulation of behavior. The findings of this research will provide an understanding of how drinkers'susceptibility to alcohol's acute behavioral-impairing effects can pose an early-onset risk factor for later alcohol dependence by promoting a continued pattern of abusive binge drinking. The research strategies also will provide methods for testing the role of neurocognitive mechanisms in the treatment efficacy of existing pharmacotherapies, such as naltrexone and acamprosate, as well as some investigational medications that might operate via neurocognitive control mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA018274-05
Application #
8515892
Study Section
Special Emphasis Panel (ZRG1-BBBP-E (02))
Program Officer
Grandison, Lindsey
Project Start
2009-09-20
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$278,483
Indirect Cost
$89,319
Name
University of Kentucky
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Weafer, Jessica; Fillmore, Mark T (2015) Alcohol-related cues potentiate alcohol impairment of behavioral control in drinkers. Psychol Addict Behav 29:290-9
Miller, Melissa A; Fillmore, Mark T (2014) Protracted impairment of impulse control under an acute dose of alcohol: a time-course analysis. Addict Behav 39:1589-96
Roberts, Walter; Peters, Jessica R; Adams, Zachary W et al. (2014) Identifying the facets of impulsivity that explain the relation between ADHD symptoms and substance use in a nonclinical sample. Addict Behav 39:1272-7
Roberts, Walter; Miller, Melissa A; Weafer, Jessica et al. (2014) Heavy drinking and the role of inhibitory control of attention. Exp Clin Psychopharmacol 22:133-40
Roberts, Walter; Milich, Richard; Fillmore, Mark T (2013) Reduced acute recovery from alcohol impairment in adults with ADHD. Psychopharmacology (Berl) 228:65-74
Miller, Melissa A; Fillmore, Mark T (2013) Can the use of multiple stop signals reduce the disinhibiting effects of alcohol? Alcohol Clin Exp Res 37:1947-53
Roberts, Walter; Fillmore, Mark T; Milich, Richard (2012) Drinking to distraction: does alcohol increase attentional bias in adults with ADHD? Exp Clin Psychopharmacol 20:107-17
Harrison, Emily L R; Fillmore, Mark T (2011) Alcohol and distraction interact to impair driving performance. Drug Alcohol Depend 117:31-7
Fillmore, Mark T; Jude, Rebecca (2011) Defining "binge" drinking as five drinks per occasion or drinking to a .08% BAC: which is more sensitive to risk? Am J Addict 20:468-75
Weafer, Jessica; Milich, Richard; Fillmore, Mark T (2011) Behavioral components of impulsivity predict alcohol consumption in adults with ADHD and healthy controls. Drug Alcohol Depend 113:139-46

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